Successfully balancing between work and family domains represents a major issue to both employees and employers, especially during COVID-19 pandemic times during which employees are often forced to work from a distance and turn to home-schooling. An occupational group particularly affected by work changes due to COVID-19 pandemic restrictions is represented by schoolteachers. We aimed at examining the associations between some job-related and family-related antecedents on the one hand and, on the other, life satisfaction as an outcome, including work–family balance as a mediator. A total of 357 Italian teachers completed a questionnaire at two different times: job control, coworkers support, supervisor support, workload, family support, and family workload were assessed at Time 1; and work–family balance and life satisfaction were assessed at Time 2. Both data collections were performed during the COVID-19 pandemic. The hypothesized direct and indirect relationships were tested by utilizing structural equation modeling. Significant and positive indirect effects of focal predictors towards life satisfaction through work–family balance were found for job control, supervisor support, and family support. The paper contributed to the literature by testing Grzywacz and Carlson’s theoretical conceptualization of work–family balance and by attempting to delineate its repertoire of potential antecedents among schoolteachers. From a practical point of view, the present study emphasizes the crucial role that certain job antecedents and family antecedents play in promoting teachers’ work–family balance and life satisfaction.